Haempphilus influenzae with a type b capsule causes serious systemic disease, particularly among young children. In addition unencapsulated H. influenzae are a cause of recurrent otitis media, an infection which can lead to hearing loss in young children. Attempts to prevent disease due to type b H. influenzae by using a vaccine of capsular material (a\polysaccharide) were not successful since very young children failed to make sufficient amounts of anticapsular antibodies. The long range goal of this research, therefore, is to determine if alternate cellular substances of H. influenzae, namely the outer membrane proteins, are suitable for use in a vaccine. An additional advantage of an outer membrane protein vaccine is that it could protect against unencapsulated as well as type b H. influenzae. On the basis of research recently completed in our laboratory, three outer membrane proteins have been selected as vaccine candidates. They each possess different but particular advantages, such as resistance to denaturation, ease of solubilization by mild (non-ionic) detergents, accessibility to antibodies in situ and cross-reactivity of accessible antigenic sites. Two types of vaccines will be made from these proteins: "conventional" vaccines of purified protein and peptide vaccines consisting of selected sequences from these proteins. The major reason for including peptide vaccines in this study is that they have the potential of overcoming some of the difficulties inherent in the use of outer membrane proteins in a vaccine. Antibodies to each vaccine preparation will be made in rabbits. The specificity and titer of the antibodies will be determined and, more importantly, their bactericidal and protective capacities. The latter will be done using the infant rat model. In addition the cross-reactivity of protective antibodies for other strains of H. influenzae, both type b and untypeable will be assayed. The protective and cross-reactive properties of the antibodies will be related to the particular proteins used in the formulation of the vaccines and to the type of formulation. Such data should be of considerable assistance in evaluating the potential of outer membrane protein vaccines and the best type of vaccine to use for prevention of H. influenzae disease. Additionally, the data obtained from these experiments should also be useful in developing strategies to prevent diseases caused by other gram-negative pathogens.